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Liposomes cancer

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https://www.readbyqxmd.com/read/28806504/designing-liposomes-to-suppress-extracellular-matrix-expression-to-enhance-drug-penetration-and-pancreatic-tumor-therapy
#1
Tianjiao Ji, Jiayan Lang, Jing Wang, Rong Cai, Yinlong Zhang, Feifei Qi, Lijing Zhang, Xiao Zhao, Wenjing Wu, Jihui Hao, Zhihai Qin, Ying Zhao, Guangjun Nie
During pancreatic tumor development, pancreatic stellate cells (PSCs) proliferate exuberantly to secrete extracellular matrix (ECM) in the tumor stroma, which presents major barriers for drug delivery and penetration in tumor tissue. Thus, down-regulating ECM levels via regulation of the PSCs may allow enhanced penetration of therapeutic drugs and thereby enhancing their therapeutic efficacy. To regulate the PSCs, a matrix metalloproteinase-2 (MMP-2) responsive peptide-hybrid liposome (MRPL) was constructed via co-assembly of a tailor-designed MMP-2 responsive amphiphilic peptide and phospholipids...
August 14, 2017: ACS Nano
https://www.readbyqxmd.com/read/28802766/a-phase-i-trial-of-intraperitoneal-gen-1-an-il-12-plasmid-formulated-with-peg-pei-cholesterol-lipopolymer-administered-with-pegylated-liposomal-doxorubicin-in-patients-with-recurrent-or-persistent-epithelial-ovarian-fallopian-tube-or-primary-peritoneal-cancers
#2
REVIEW
Premal H Thaker, William E Brady, Heather A Lankes, Kunle Odunsi, William H Bradley, Kathleen N Moore, Carolyn Y Muller, Khursheed Anwer, Russell J Schilder, Ronald D Alvarez, Paula M Fracasso
OBJECTIVE: The study's purpose was to assess safety and efficacy of escalating doses of weekly GEN-1 with pegylated liposomal doxorubicin (PLD) in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers (EOC). METHODS: Patients had persistent or recurrent platinum-resistant EOC. The trial was a standard 3+3 phase I dose escalation design with patients receiving intravenous PLD 40mg/m(2) (dose level 1 and 2) or 50mg/m(2) (dose level 3) every 28days and intraperitoneal GEN-1 at 24mg/m(2) (dose level 1) or 36mg/m(2) (dose level 2 and 3) on days 1, 8, 15, and 22 of a 28day cycle...
August 9, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28801766/absence-of-cardiotoxicity-with-prolonged-treatment-and-large-accumulating-doses-of-pegylated-liposomal-doxorubicin
#3
N Blank, I Laskov, R Kessous, L Kogan, S Lau, I A Sebag, Walter H Gotlieb, L Rudski
BACKGROUND: Pegylated liposomal doxorubicin (PLD) is used as a second-line therapy for gynecologic cancers, with a better short-term toxicity profile compared to doxorubicin or other anthracyclines. METHODS: We screened 14 patients with recurrent gynecologic cancers, who underwent prolonged treatment with large cumulative doses of PLD for overt or subtle signs of cardiotoxicity (CTX) using standard and advanced echocardiography techniques [3D volumetric method for left ventricular ejection fraction (LVEF) and left ventricular/right ventricular global longitudinal strain]...
August 11, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28797563/binding-of-a-type-1-rip-and-of-its-chimeric-variant-to-phospholipid-bilayers-evidence-for-a-link-between-cytotoxicity-and-protein-membrane-interactions
#4
Elio Pizzo, Rosario Oliva, Rita Morra, Andrea Bosso, Sara Ragucci, Luigi Petraccone, Pompea Del Vecchio, Antimo Di Maro
Ribosome-inactivating proteins (RIPs) are enzymes, almost all identified in plants, able to kill cells by depurination of rRNAs. Recently, in order to improve resistance to proteolysis of a type 1 RIP (PD-L4), we produced a recombinant chimera combining it with a wheat protease inhibitor (WSCI). Resulting chimeric construct, named PD-L4UWSCI, in addition to present the functions of the two domains, shows also an enhanced cytotoxic action on murine cancer cells when compared to PD-L4. Since different ways of interaction of proteins with membranes imply different resulting effects on cells, in this study we investigate conformational stability of PD-L4 and PD-L4UWSCI and their interaction with membrane models (liposomes)...
August 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28795851/selective-induction-of-apoptosis-in-mcf7-cancer-cell-by-targeted-liposomes-functionalized-with-mannose-6-phosphate
#5
Cristina Minnelli, Laura Cianfruglia, Emiliano Laudadio, Roberta Galeazzi, Michela Pisani, Emanuela Crucianelli, Davide Bizzaro, Tatiana Armeni, Giovanna Mobbili
Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalization and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28790822/complement-c3-dependent-uptake-of-targeted-liposomes-into-human-macrophages-b-cells-dendritic-cells-neutrophils-and-mdscs
#6
Alexandra Francian, Kristine Mann, Max Kullberg
Antitumor immunity in cancer patients is heavily modulated by cells of the innate immune system. Antigen-presenting cells, including dendritic cells, macrophages, and B cells, initiate immune recognition of tumor antigen by displaying antigen to effector cells. Countering this immune stimulation are immunosuppressive cells which include M2 macrophages, N2 neutrophils, and myeloid-derived suppressor cells (MDSCs). To create effective cancer immunotherapies, it is critical that we can target these important cell types of the immune system with immunostimulatory compounds...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28789523/efficient-sirna-delivery-by-lipid-nanoparticles-modified-with-a-non-standard-macrocyclic-peptide-for-epcam-targeting
#7
Yu Sakurai, Wataru Mizumura, Manami Murata, Tomoya Hada, Shoshiro Yamamoto, Kenichiro Ito, Kazuhiro Iwasaki, Takayuki Katoh, Yuki Goto, Asako Takagi, Michinori Kohara, Hiroaki Suga, Hideyoshi Harashima
The development of a specific, effective method for the delivery of therapeutics including small molecules and nucleic acids to tumor tissue remains to be solved. Numerous types of lipid nanoparticles (LNPs) have been developed in attempts to achieve this goal. However, LNPs are probably not taken up by target cells because cancer-targeting LNPs are typically modified with poly(ethylene glycol) (PEG), which inhibit the cellular uptake of LNPs, to passively accumulate in tumor tissue via the enhanced permeability and retention (EPR) effect...
August 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28777336/development-of-ph-sensitive-dextran-derivatives-with-strong-adjuvant-function-and-their-application-to-antigen-delivery
#8
Eiji Yuba, Shinya Uesugi, Maiko Miyazaki, Yuna Kado, Atsushi Harada, Kenji Kono
To achieve efficient cancer immunotherapy, the induction of cytotoxic T lymphocyte-based cellular immunity is necessary. In order to induce cellular immunity, antigen carriers that can deliver antigen into cytosol of antigen presenting cells and can activate these cells are required. We previously developed 3-methyl glutarylated dextran (MGlu-Dex) for cytoplasmic delivery of antigen via membrane disruption ability at weakly acidic pH in endosome/lysosomes. MGlu-Dex-modified liposomes delivered model antigens into cytosol of dendritic cells and induced antigen-specific cellular immunity...
August 4, 2017: Membranes
https://www.readbyqxmd.com/read/28774852/enhanced-efficacy-of-anti-mir-191-delivery-through-stearylamine-liposome-formulation-for-the-treatment-of-breast-cancer-cells
#9
Shivani Sharma, Vinoth Rajendran, Ritu Kulshreshtha, Prahlad C Ghosh
MicroRNAs are gaining rapid attention as promising targets for cancer treatment; however, efficient delivery of therapeutic miRNA or anti-miRNA into cancer cells remains a major challenge. Our previous work identified miR-191 as an oncogenic miRNA overexpressed in breast cancer that assists in progression of malignant transformation. Thus, inhibition of miR-191 using antisense miR-191 (anti-miR-191) has immense therapeutic potential. Here, we have developed a stearylamine (SA) based cationic liposome for delivery of miR-191 inhibitor (anti-miR-191), and studied its efficacy in breast cancer cells (MCF-7 and ZR-75-1) in culture...
July 31, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28763612/cyclic-peptoids-as-mycotoxins-mimics-an-exploration-of-their-structural-and-biological-properties
#10
Assunta D'Amato, Raffaele Volpe, Maria C Vaccaro, Stefania Terracciano, Ines Bruno, Massimo Tosolini, Consiglia Tedesco, Giovanni Pierri, Paolo Tecilla, Chiara Costabile, Giorgio Della Sala, Irene Izzo, Francesco De Riccardis
Cyclic peptoids have recently emerged as important examples of peptidomimetics for their interesting complexing properties and innate ability to permeate biological barriers. In the present contribution, experimental and theoretical data evidence the intricate conformational and stereochemical properties of five novel hexameric peptoids decorated with N-iso-propyl, N-iso-butyl and N-benzyl substituents. Complexation studies by NMR, in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), theoretical calculations and single crystal X-ray analyses indicate that the conformationally stable host/guest metal adducts display architectural ordering comparable to that of the enniatins and beauvericin mycotoxins...
August 1, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28761344/synergistic-apoptotic-effects-of-apigenin-tpgs-liposomes-and-tyroservatide-implications-for-effective-treatment-of-lung-cancer
#11
Xin Jin, Qing Yang, Youwen Zhang
To develop an alternative treatment for lung cancer, a combination of two potent chemotherapeutic agents - liposomal apigenin and tyroservatide - was developed. The therapeutic potential of this combination was investigated using A549 cells. Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to tumor cells, both in vitro and in vivo. Importantly, compared to either agent alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer cell invasion at a lower dose...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28760449/tumor-microenvironment-determines-response-to-a-heat-activated-thermosensitive-liposome-formulation-of-cisplatin-in-cervical-carcinoma
#12
Yannan N Dou, Naz Chaudary, Martin C Chang, Michael Dunne, Huang Huang, David A Jaffray, Michael Milosevic, Christine Allen
Significant heterogeneity in the tumor microenvironment of human cervical cancer patients is known to challenge treatment outcomes in this population. The current standard of care for cervical cancer patients is radiation therapy and concurrent cisplatin (CDDP) chemotherapy. Yet this treatment strategy fails to control loco-regional disease in 10-30% of patients. In order to improve the loco-regional control rate, a thermosensitive liposome formulation of CDDP (HTLC) was developed to increase local concentrations of drug in response to mild hyperthermia (HT)...
July 29, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28760000/cholesterol-derivative-based-liposomes-for-gemcitabine-delivery-preparation-in-vitro-and-in-vivo-characterization
#13
Tang Li, Li Chen, Yihui Deng, Xinrong Liu, Xiaoyun Zhao, Yiwen Cui, Jia Shi, Rui Feng, Yanzhi Song
As an anti-tumor drug, gemcitabine (Gem) is commonly used for the treatment of non-small cell lung cancer and pancreatic cancer. However, there are several clinical drawbacks to using Gem, including its extremely short plasma half-life and side effects. To prolong its half-life and reduce its side effects, we synthesized a derivative of Gem using cholesterol (Chol). This derivative, called gemcitabine-cholesterol (Gem-Chol) was entrapped into liposomes by a thin-film dispersion method. The particle size of the Gem-Chol liposomes was 112...
August 1, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28756613/phase-ii-study-of-paclitaxel-associated-with-lipid-core-nanoparticles-lde-as-third-line-treatment-of-patients-with-epithelial-ovarian-carcinoma
#14
Silvia R Graziani, Carolina G Vital, Aleksandra T Morikawa, Brigitte M Van Eyll, Hezio J Fernandes Junior, Roberto Kalil Filho, Raul C Maranhão
Ovarian cancer is often diagnosed at advanced stages, when poorly responsive to standard treatment. First-line treatment consists in schemes including cytoreductive surgery followed by adjuvant chemotherapy schemes with platinum and taxane derivatives. Second-line regimens are based on gemcitabine and liposomal doxorubicin. Third line is often not worthwhile because of the high toxicity with poor response to treatment. Previously, we showed that paclitaxel (PTX) carried in non-protein lipid core nanoparticles (LDE) resembling the chemical structure of LDL has remarkably reduced toxicity...
September 2017: Medical Oncology
https://www.readbyqxmd.com/read/28754610/secretory-phospholipase-a2-responsive-liposomes-exhibit-a-potent-anti-neoplastic-effect-in-vitro-but-induce-unforeseen-severe-toxicity-in-vivo
#15
Ragnhild Garborg Østrem, Ladan Parhamifar, Houman Pourhassan, Gael Clergeaud, Ole Lerberg Nielsen, Andreas Kjær, Anders Elias Hansen, Thomas Lars Andresen
The clinical use of liposomal drug delivery vehicles is often hindered by insufficient drug release. Here we present the rational design of liposomes optimized for secretory phospholipase A2 (sPLA2) triggered drug release, and test their utility in vitro and in vivo. We hypothesized that by adjusting the level of cholesterol in anionic, unsaturated liposomes we could tune the enzyme specificity based on membrane fluidity, thus obtaining liposomes with an improved therapeutic outcome and reduced side effects...
July 25, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28752187/systematic-review-and-network-meta-analysis-comparing-palbociclib-with-chemotherapy-agents-for-the-treatment-of-postmenopausal-women-with-hr-positive-and-her2-negative-advanced-metastatic-breast-cancer
#16
Florence R Wilson, Abhishek Varu, Debanjali Mitra, Chris Cameron, Shrividya Iyer
PURPOSE: To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment for advanced disease (first line) or whose disease progressed after prior endocrine therapy or chemotherapy (second line). METHODS: A systematic search identified randomized controlled trials (RCTs) published from January 2000 to January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or chemotherapy agents + biological therapies in the first- and second-line treatment of postmenopausal women with HR+/HER2- ABC/MBC...
July 27, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28751117/single-agent-trabectedin-in-heavily-pretreated-patients-with-recurrent-ovarian-cancer
#17
Jean-Philippe Adam, Feriel Boumedien, Nathalie Letarte, Diane Provencher
PURPOSE: In 2012, due to a shortage of pegylated liposomal doxorubicin, single agent trabectedin was proposed as an alternative of treatment to our patients with recurrent ovarian cancer (ROC) at our center. The aim of this retrospective study was to evaluate efficacy and tolerability of trabectedin in this context. PATIENTS AND METHODS: This retrospective study included all patients who received intravenous trabectedin 1.3mg/m(2) over 3h every 3weeks for ROC between January 2012 and December 2015 at the Centre hospitalier de l'Université de Montreal...
July 21, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28743635/molecular-imaging-in-drug-development-update-and-challenges-for-radiolabeled-antibodies-and-nanotechnology
#18
REVIEW
Ilaria Colombo, Marta Overchuk, Juan Chen, Raymond M Reilly, Gang Zheng, Stephanie Lheureux
Despite the significant advancement achieved in understanding the molecular mechanisms responsible for cancer transformation and aberrant proliferation, leading to novel targeted cancer therapies, significant effort is still needed to "personalize" cancer treatment. Molecular imaging is an emerging field that has shown the ability to characterize in vivo the molecular pathways present at the cancer cell level, enabling diagnosis and personalized treatment of malignancies. These technologies, particularly SPECT and PET also permit the development of novel radiotheranostic probes, which provide capabilities for diagnosis and treatment with the same agent...
July 22, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28743554/solubilization-of-%C3%AE-galactosylceramide-in-aqueous-medium-impact-on-natural-killer-t-cell-activation-and-antitumor-responses
#19
Elodie Macho-Fernandez, Neila Chekkat, Christophe Ehret, Jean-Sébastien Thomann, Marcella De Giorgi, Maria Vittoria Spanedda, Line Bourel-Bonnet, Didier Betbeder, Béatrice Heurtault, Christelle Faveeuw, Sylvie Fournel, Benoît Frisch, François Trottein
The potent antitumor effect of α-galactosylceramide (α-GalCer) is based on its recognition by invariant Natural Killer T cells (iNKT) after its capture and presentation by antigen presenting cells including dendritic cells (DCs). Synthetic α-GalCer has already been tested in advanced cancer patients but no or only moderate clinical responses were obtained. To optimize α-GalCer efficacy, we have postulated that alternative formulations impacting its molecular organization in aqueous medium could modify DC uptake and iNKT-based immune responses...
July 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28741634/mitochondria-targeting-near-infrared-light-triggered-thermosensitive-liposomes-for-localized-photothermal-and-photodynamic-ablation-of-tumors-combined-with-chemotherapy
#20
Caixia Yue, Yuming Yang, Jie Song, Gabriel Alfranca, Chunlei Zhang, Qian Zhang, Ting Yin, Fei Pan, Jesús M de la Fuente, Daxiang Cui
Lonidamine, an anticancer drug that acts on mitochondria, has poor water solubility. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Hence, a mitochondria-targeting drug delivery system loaded with Lonidamine and a ROS-produced photosensitizer could improve the bioavailability of Lonidamine and maximize photodynamic therapeutic efficiency. Here we report, for the first time, new IR-780 and Lonidamine encapsulated mitochondria-targeting thermosensitive liposomes (IL-TTSL)...
July 25, 2017: Nanoscale
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